ROS-induced ZNF580 expression: a key role for H2O2/NF-κB signaling pathway in vascular endothelial inflammation

Mol Cell Biochem. 2012 Jan;359(1-2):183-91. doi: 10.1007/s11010-011-1013-0. Epub 2011 Aug 10.

Abstract

ZNF580, a newly found C2H2 zinc finger transcription factor, was first described by Zhang (GenBank ID: AF184939). Emerging evidence has suggested that reactive oxygen species (ROS) play an important role in redox-sensitive signal transduction, and the vascular endothelium plays a critical role in the vascular inflammatory response. In this communication, we present evidence for the potential role of ZNF580 in hydrogen peroxide (H2O2)-regulated inflammation-related signaling pathways. In a human endothelial cell hybridoma line (EA.hy926), ZNF580 levels were markedly upregulated with H2O2 stimulation in different concentrations (0-400 μM) and at different time-points (0-6 h). H2O2 promoted the rapid translocation of p65 from the cytoplasm into the nucleus according to immunocytochemistry staining. In subsequent research, inhibition of NF-κB by pyrrolidine dithiocarbamate (PDTC, a selective chemical inhibitor of NF-κB) was shown to block the upregulated expression of ZNF580 that was induced by H2O2. Furthermore, transient transfection of ZNF580 resulted in an increase of the pro-inflammatory cytokine interleukin-8 (IL-8) 3.01±0.05 folds according to real-time RT-PCR and ELISA assays, which also showed significantly enhanced motility of human acute monocytic leukemia cells (THP-1). These results suggest that H2O2 upregulates the expression of ZNF580 via the NF-κB signaling pathway, and overexpression of ZNF580 plays a critical role in augmenting the release of pro-inflammatory cytokine IL-8.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Endothelium, Vascular / pathology*
  • Humans
  • Hydrogen Peroxide / metabolism
  • Hydrogen Peroxide / pharmacology
  • Inflammation / metabolism*
  • Interleukin-8
  • NF-kappa B / metabolism*
  • Reactive Oxygen Species / pharmacology
  • Signal Transduction / physiology*
  • Transcription Factors / biosynthesis*
  • Up-Regulation / drug effects

Substances

  • Interleukin-8
  • NF-kappa B
  • Reactive Oxygen Species
  • Transcription Factors
  • ZNF580 protein, human
  • Hydrogen Peroxide